LUCAT1 Knockdown Research Articles

LUCAT1 Activates the Malignant Phenotypes of Lung Cancer Cells via Regulating P53 Ubiquitination.

Long non-coding RN (lncRNAs) have been implicated in lung cancer, but the mechanisms stay unclear. We investigated the theatrical role and mechanism of lncRNA Lung cancer associated transcript 1 LUCAT1 in the malignant progress of lung cancer. From May 2022 to March 2023, a total of thirty normal and cancerous tissues were collected from patients diagnosed with non-small cell lung cancer at Zhongke Gengjiu Hospital in Anhui Province, China. The human SPC-A1 and A549 cell lines were chosen as the subjects for the relevant cellular experiments in this study. LncRNAs were expressed in a different manner identified by bioinformatics methods, and the expression levels in lung cancer tissues as well as cells were verified by the qRT-PCR assay. The biological role of LUCAT1 in NSCLC was determined by CCK-8, EdU, and transwell assay. The regulation of ubiquitin of P53 by LUCAT1 was studied, which showed that LUCAT1 was significantly elevated in NSCLC cell lines and patients' tissues (P<0.05). High levels of LUCAT1 promoted the proliferation, invasion, and migration of NSCLC cells. Mechanism studies showed that LUCAT1 was mainly located in the nucleus, which bound to P53 and mediated the ubiquitinated degradation of P53. Meanwhile, LUCAT1 knockdown attenuated the ubiquitination process of P53. In addition, rescue experiments illustrated that LUCAT1 induced the proliferation and invasion of NSCLC cells, and played a key role in the survival and tumorigenicity of NSCLC cells by mediating the ubiquitination of P53. Collectively, LUCAT1 activated the malignant phenotypes of NSCLC cells via regulating P53 ubiquitination, which provided a new idea for the diagnosis and treatment of NSCLC.

Retraction Note: Knockdown of long non-coding RNA LUCAT1 reverses high glucose-induced cardiomyocyte injury via targeting CYP11B2.

The article "Knockdown of long non-coding RNA LUCAT1 reverses high glucose-induced cardiomyocyte injury via targeting CYP11B2, by Y. Yin, Z.-F. Yang, X.-H. Li, L.-Q. Zhou, Y.-J. Zhang, B. Yang, published in Eur Rev Med Pharmacol Sci 2019; 23 (19): 8560-8565-DOI: 10.26355/eurrev_201910_19171-PMID: 31646588" has been retracted by the authors as they cannot ensure the reproducibility of the data. The third party who provided some data turned out to be unreliable. The same manuscript was also questioned on PubPeer after publication. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19171.

Knockdown of lncRNA LUCAT1 attenuates sepsis‑induced myocardial cell injury by sponging miR-642a.

The heart is one of the most common organs involved in sepsis-induced organ dysfunction and about 50% septic patients complicated with myocardial injury. So far, the molecular mechanisms underlying sepsis-induced cardiac damage remain unclear. In this study we aimed to evaluate the effect of miR-642a on sepsis-induced cardiac injury in vitro and explore the possible lncRNA-microRNA mechanism. We first downloaded GSE101639 to identify differentially expressed genes (DEGs) in sepsis. The expression of miR-642a in LPS-induced H9C2 cells was detected by qRT-PCR. MTT assay, cell migration, flow cytometry analysis, ELISA, qRT-PCR and Western blotting analysis were applied to evaluating the effect of miR-642a mimic on LPS-induced H9C2 cells. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism. The results showed miR-642a expression was decreased in septic patients and LPS-induced H9C2 cells. Besides, MiR-642a mimic promoted cell viability and migration, inhibited cell apoptosis of LPS-induced H9C2 cells. Bioinformatics analysis showed miR-642a directly targets with 3'-UTR of ROCK1. Moreover, LUCAT1 regulated ROCK1 expression act as a competing endogenous RNA (ceRNA) for miR-642a. Our data demonstrated that lncRNA LUCAT1 could function via sponging miR-642a to regulate ROCK1 expression in LPS-induced H9C2 cells. And knockdown of lncRNA LUCAT1 could suppress LPS-induced cardiac injury in vitro.

LUCAT1 as an oncogene in tongue squamous cell carcinoma by targeting miR-375 expression.

Emerging studies suggested that lncRNAs play a crucial molecular role in cancer development and progression. LncRNA LUCAT1 has been proved as oncogenic molecular in lung cancer, glioma, osteosarcoma, renal carcinoma and oesophageal squamous cell carcinoma. However, its roles and function mechanisms in tongue squamous cell carcinoma (TSCC) are still unknown. We showed that the expression of LUCAT1 was up‐regulated in the TSCC cells and tissues and the higher LUCAT1 expression was associated with the poor overall survival (OS). Knockdown expression of LUCAT1 suppressed TSCC cell proliferation, cycle and migration. In addition, we demonstrated that miR‐375 overexpression inhibited the luciferase activity of LUCAT1 wild‐type and knockdown LUCAT1 promoted the miR‐375 expression in TSCC cell. Furthermore, we indicated that miR‐375 expression was down‐regulated in the TSCC cell lines and tissues and the lower expression of miR‐375 was associated with poor OS. The expression of miR‐375 was inversely correlated with LUCAT1 expression in the TSCC tissues. Knockdown LUCAT1 promoted TSCC cell proliferation, cell cycle and migration partly through regulating miR‐375 expression. In summary, this study suggested the tumorigenic effect of lncRNA LUCAT1 in TSCC cells by targeting miR‐375 expression.

Knockdown of the Long Noncoding RNA LUCAT1 Inhibits High-Glucose-Induced Epithelial-Mesenchymal Transition through the miR-199a-5p-ZEB1 Axis in Human Renal Tubular Epithelial Cells.

Renal fibrosis, the leading cause of end-stage renal disease and in which epithelial-mesenchymal transition (EMT) plays a central role, has a complex pathogenesis that is not fully understood. Therefore, we investigated the role of the long noncoding RNA LUCAT1 in the EMT of renal tubular epithelial cells under high-glucose (HG) conditions and the underlying mechanism involved. In this study, we established HG and normal glucose groups of HK-2 cells by treating HK-2 cells 30.0 or 5.5 mmol/L glucose, respectively. To investigate the roles of LUCAT1 and miR-199a-5p in HG-induced EMT, we transfected the HG group with negative control small interfering RNA (siRNA), siRNA targeting LUCAT1, negative control microRNA, or an miR-199a-5p mimic. The results of the quantitative reverse transcription PCR indicated that the LUCAT1 level in the HG group was increased, whereas the miR-199a-5p level was decreased. The EMT in the cells was induced by treatment with HG but was weakened by LUCAT1 knockdown or miR-199a-5p overexpression, which both also inhibited the HG-induced phosphorylation of SMAD3. Moreover, LUCAT1 and ZEB1 mRNA comprised the same microRNA response elements of miR-199a-5p. LUCAT1 knockdown had no effect on the miR-199a-5p level but decreased the HG-induced upregulation of ZEB1. In conclusion, HG conditions induced the upregulation of LUCAT1, and LUCAT1 knockdown inhibited the EMT in HG-treated HK-2 cells. LUCAT1 likely promotes HG-induced EMT through ZEB1 by sponging miR-199a-5p.

LncRNA LUCAT1/miR-181a-5p axis promotes proliferation and invasion of breast cancer via targeting KLF6 and KLF15

BackgroundLong non-coding RNAs (lncRNAs) are novel regulatory molecules in breast cancer development. LncRNA LUCAT1 is a potential tumor promoter in human cancers. In this study, we aimed to explore the role of LUCAT1 in human breast cancer tissues and cells.MethodsA total of 31 breast cancer patients who underwent tumor resection, but without chemo- or radiotherapy or acute lung/heart/kidney diseases, provided tumor and adjacent normal tissues. Bioinformatic analysis, qRT-PCR, and luciferase reporter assay were carried out during the study.ResultsqRT-PCR analysis indicated that, compared with the adjacent tissues and MCF-10A normal breast epithelial cells, LUCAT1 was markedly up-regulated in the breast cancer tissues and five BC cell lines, including MDA-MB-231, MDA-MB-468, MDA-MB-435, SKBR3, and MCF-7. The knockdown of LUCAT1, through the transfection of small interfering RNA (siRNA) specific to LUCAT1, resulted in inhibition of proliferation in breast cancer cells. The expression levels of miR-181a-5p were decreased in the breast cancer tissues and five BC cell lines. Bioinformatic analysis and luciferase reporter assay suggested the interaction between miR-181a-5p and LUCAT1. In addition, the effects of LUCAT1 on promoting cell proliferation were attenuated by overexpression of miR-181a-5p through the transfection of miR-181a-5p mimic. Moreover, bioinformatics and luciferase reporter assay confirmed that miR-181a-5p targeted the 3′-UTR region of KLF6 and KLF15 mRNA, which were two tumor suppressor genes. LUCAT1/miR-181a-5p axis regulated the expression of KLF6 and KLF15 both in vitro and in vivo.ConclusionsOur data indicate that LUCAT1/miR-181a-5p axis can serve as a novel therapeutic target in breast cancer.

Hypoxia induced LUCAT1/PTBP1 axis modulates cancer cell viability and chemotherapy response

BackgroundHypoxic tumors are refractory to DNA damage drugs. However, the underlying mechanism has yet to be elucidated. We aimed to identify lncRNAs that upregulated under hypoxia and their effects on colorectal cancer (CRC).MethodsCRC cells were treated with 1% O2 to identify lncRNAs that upregulated under hypoxia. We integrated these lncRNAs with RNA-seq of 4 paired CRC tissues and TCGA data to get candidate lncRNAs. Multiple in vitro and in vivo assays were used to explore the role of LUCAT1 in CRC.ResultsWe identified a hypoxia-induced lncRNA LUCAT1 that facilitated the growth of CRC cells and contributed to drug resistance of CRC cells both in vitro and in vivo. Mechanically, LUCAT1 interacts with polypyrimidine tract binding protein 1 (PTBP1) in CRC cells, facilitates the association of a set of DNA damage related genes with PTBP1, thus resulting in altered alternative splicing of these genes. Moreover, ectopic expression of PTBP1 in CRC cells with knockdown of LUCAT1 abrogated the effects induced by LUCAT1 knockdown. Chemotherapeutics drug combined with LUCAT1 knockdown via antisense oligonucleotides (ASO) would get a better outcome in vivo, compared with group treated with chemotherapeutic drug only. Notably, LUCAT1 is upregulated in CRC tissues, compared to adjacent normal tissues; and CRC patients with higher LUCAT1 have a worse prognosis and poorly responded to chemotherapy in the clinic.ConclusionsOur data suggested CRC cells utilizes LUCAT1 to develop resistance to DNA damage drugs, and disrupting the LUCAT1/PTBP1 axis might be a promising therapeutic strategy for refractory hypoxic tumors.

LncRNA LUCAT1 contributes to cell proliferation and migration in human pancreatic ductal adenocarcinoma via sponging miR-539.

Pancreatic ductal adenocarcinoma is one of the most aggressive and dreadful malignancies worldwide. Long noncoding RNAs (lncRNAs) have emerged as vital regulators in the development of human malignancies and other disorders. This study aimed to characterize the role of lncRNA lung cancer‐associated transcript 1 (lncRNA LUCAT1), a novel cancer‐related lncRNA, in human PDAC. Here we initially analyzed the expression patterns of lncRNA LUCAT1 and evaluated its clinical significance. The qRT‐PCR analysis and in situ hybridization staining showed that lncRNA LUCAT1 expression was significantly increased in tumorous tissues compared with adjacent normal tissues. Additionally, we found that increased lncRNA LUCAT1 expression was linked to larger tumor size and lymphatic invasion. Consistently, lncRNA LUCAT1 was remarkably up‐regulated in PDAC cell lines. To better understand the biological role of lncRNA LUCAT1, we evaluated the effects of lncRNA LUCAT1 knockdown on PDAC cell proliferation, cell cycle progression, migration, and invasion using MTT assays, flow cytometry, Transwell migration, and invasion assays, respectively. Functional studies demonstrated that lncRNA LUCAT1 knockdown dramatically suppressed PDAC cell proliferation, induced cell cycle arrest and inhibited cell migration and invasion. Tumor xenograft in vivo assays displayed that lncRNA LUCAT1 inhibited tumorigenecity of PDAC cells. Mechanistic studies uncovered that lncRNA LUCAT1 acted as a molecular sponge of miR‐539 and that miR‐539 mediated the effects of lncRNA LUCAT1 on PDAC cell proliferation, cell cycle progression, and motility. Collectively, our findings may offer some novel insights into understanding lncRNA LUCAT1 in PDAC.

LncRNA LUCAT1 as a novel prognostic biomarker for patients with papillary thyroid cancer

In recent years, long non-coding RNAs have emerged as a novel class of regulators of cancer biological processes. While they are dysregulated in many cancer types, little is known about their expression and functional profiles. This study has been focused on the determination of the role of a specific lncRNA in papillary thyroid cancer. Quantitative reverse transcription PCR was performed to detect the expression levels of 84 lncRNAs in 61 papillary thyroid carcinoma tissues and their adjacent non-tumor tissues. The highest fold-change was obtained for lung cancer associated transcript 1 LUCAT1, and thus, this study determines the expression and biological implication of lncRNA LUCAT1 through different in vitro and ex vivo approaches in this tumor. LUCAT1 was specifically located at the cell nucleus in tumoral regions of patient tissues. Furthermore, LUCAT1 knockdown significantly reduced both cell proliferation and invasion ex vivo and induced cell-cycle arrest and apoptosis. These facts were corroborated by an enhanced expression of P21, P57, P53 and BAX, and a reduced expression of EZH2 and HDAC1. In addition, a significant decrease was observed on DNMT1 and NRF2 genes, helping to clarify the role of LUCAT1 on PTC. Our study reveals the involvement of LUCAT1 in PTC development, through acting in cell-cycle regulation, proliferation, epigenetic modifications through LUCAT1/ CDK1/ EZH2/ P57/ P21/ HDAC1/ DNMT1/ P53/ BAX axis and apoptosis, via extrinsic pathway activating caspases. These findings indicate that LUCAT1 is maybe a potential therapeutic target and molecular biomarker for PTC.

Knockdown of long non-coding RNA LUCAT1 reverses high glucose-induced cardiomyocyte injury via targeting CYP11B2.

Diabetic cardiomyopathy (DCM) is one of the major complications in patients with diabetes mellitus. Recently, long noncoding RNAs (lncRNAs) have been well concerned for their roles in the progression of multiple diseases, including DCM. In this research, we aimed to explore the role of lncRNA LUCAT1 in cardiomyocyte injury and apoptosis induced by high glucose (HG) in vitro. High glucose-induced (HG-induced) AC16 cardiomyocytes transfected with LUCAT1 shRNA were constructed. LUCAT1 expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Subsequently, cell proliferation and cell apoptosis were detected after LUCAT1 knockdown in HG-induced AC16 cells. Moreover, RT-qPCR and Western blot assay were performed to explore the potential underlying mechanism of LUCAT1 in DCM. The expression of LUCAT1 was significantly upregulated in HG-treated AC16 cardiomyocytes. Moreover, knockdown of LUCAT1 could reverse cardiomyocyte injury and apoptosis through downregulating CYP11B2. We first demonstrated that knockdown of LUCAT1 could reverse HG-induced cardiomyocyte injury by down-regulating CYP11B2. Our findings might offer a new direction for interpreting the mechanism of DCM development.

Long non-coding RNA LUCAT1 promotes proliferation and invasion in gastric cancer by regulating miR-134-5p/YWHAZ axis

PurposeThe aim of this study was to research the function of lncRNA LUCAT1 in gastric cancer. MethodsHuman gastric cancer tissues and paracancer tissues were obtained from 98 patients undergoing surgical resection in our hospital. The human gastric cancer cell lines (HGC27, BGC823, MGC803, SGC7901 and AGS), and normal gastric mucosal cell line GSE1 were used to research the role of lncRNA LUCAT1. ShRNAs specifically targeting lncRNA LUCAT1, miR-134-5p mimic, miR-134-5p inhibitor and their related controls were transfected into cells. Quantitative real-time PCR was used to detect the expression of lncRNA LUCAT1, miR-134-5p and YWHAZ. The cell proliferation of SGC7901 cells was determined by CCK8 kit. Colony formation assay was undertaken. Cell apoptosis assay was processed using the Annexin V-FITC / propidium iodide (annxinV/PI) apoptosis detection kit. Migration and invasion were detected by transwell assay. Tumor xenograft model was conducted to calculate the size and weight of the tumors. Luciferase reporter assay was used to confirm the interactions among lncRNA LUCAT1, miR-134-5p and YWHAZ. ResultsLncRNA LUCAT1 was confirmed to be highly expressed in gastric cancer. Patients with high LUCAT1 level displayed short overall survival and disease-free survival periods. LUCAT1 knockdown or miR-134-5p overexpression decreased the proliferation, colony formation, migration and invasion of SGC7901 cells. ConclusionsLncRNA LUCAT1 could promote proliferation and invasion of gastric cancer by regulating miR-134-5p/YWHAZ axis.

LncRNA LUCAT1 promotes rowth, migration, and invasion of oral squamous cell carcinoma by upregulating PCNA.

Recent studies have revealed the important role of long noncoding RNAs (lncRNAs) in the progression of tumorigenesis. This study aims to identify how lncRNA LUCAT1 functions in the progression of OSCC (oral squamous cell carcinoma). Relative expression of lncRNA LUCAT1 in both OSCC cells and 50 paired tissue samples was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Moreover, biological function of LUCAT1 in OSCC was identified by performing transwell assay, wound healing assay and proliferation assay in vitro. The underlying mechanism was explored by qRT-PCR and Western blot. LUCAT1 expression was remarkably downregulated in OSCC tissues when compared with that in adjacent normal samples. Moreover, proliferation, invasion and migration of OSCC cells were inhibited after knockdown of LUCAT1 in vitro. Knockdown of LUCAT1 downregulated PCNA in OSCC cells at mRNA and protein level in vitro. Besides, PCNA expression in OSCC tissues was positively correlated with the expression of LUCAT1. Knockdown of LUCAT1 could inhibit migration, invasion and proliferation capacities of OSCC cells through downregulating PCNA, which may offer a new therapeutic intervention for OSCC patients.

The long noncoding RNA LUCAT1 promotes tumorigenesis by controlling ubiquitination and stability of DNA methyltransferase 1 in esophageal squamous cell carcinoma

Available targeted therapies for esophageal squamous cell carcinoma (ESCC) are limited; thus, further genetic and epigenetic studies are needed. Recently, many long noncoding RNAs (lncRNAs) have been reported to be involved in various cancers. Here, we investigated whether the lncRNA LUCAT1 was related to the carcinogenesis of ESCC based on previous studies in lung cancer. LUCAT1 was significantly upregulated in ESCC cell lines and cancer tissue compared with normal cells and adjacent normal tissues. LUCAT1 knockdown reduced cell proliferation, induced apoptosis, and upregulated tumor-suppressor genes by reducing DNA methylation in KYSE-30 cells. Moreover, LUCAT1 siRNA reduced DNA methyltransferase 1 (DNMT1) protein levels without affecting transcription. Patients with high LUCAT1 expression had significantly lower survival rates than patients with low LUCAT1 expression. Our results thus suggest that LUCAT1 regulates the stability of DNMT1 and inhibits the expression of tumor suppressors through DNA methylation, leading to the formation and metastasis of ESCC. We identified LUCAT1 as a potential target for drug development and as a biomarker for ESCC.

Long non-coding RNA LUCAT1 modulates methotrexate resistance in osteosarcoma via miR-200c/ABCB1 axis

Long non-coding RNAs (lncRNAs) have been verified to participate in the tumorigenesis of multiple cancers. Nevertheless, the deepgoing role molecular mechanisms of lncRNAs on osteosarcoma chemoresistance remain unclear. In present study, we investigate the function of lncRNA LUCAT1 on osteosarcoma methotrexate (MTX) resistant phenotype and discover the potential regulatory mechanism. Results showed that LUCAT1 was up-regulated in MTX-resistant cells (MG63/MTX, HOS/MTX) compared to that in parental cells. LncRNA LUCAT1 and ABCB1 protein expression levels were both up-regulated when induced by different concentration of methotrexate. In vitro and vivo, LUCAT1 knockdown decreased the expression levels drug resistance related genes (MDR1, MRP5, LRP1), proliferation, invasion and tumor growth of osteosarcoma cells. Bioinformatics tools and luciferase assay reveled that miR-200c both targeted the 3′-UTR of LUCAT1 and ABCB1 mRNA, suggesting the modulation of LUCAT1 on ABCB1 through sponging miR-200c. Rescue experiments confirmed the combined role of LUCAT1, miR-200c and ABCB1 on osteosarcoma proliferation, invasion and methotrexate resistance. Overall, results indicate the vital role of LUCAT1 in the methotrexate resistance regulation through miR-200c/ABCB1 pathway, providing a novel insight and treatment strategy for osteosarcoma drug resistance.

Identification of dysregulated lncRNAs profiling and metastasis-associated lncRNAs in colorectal cancer by genome-wide analysis.

The colorectal cancer (CRC) is one of the leading causes of cancer‐related death worldwide, but the pathogenesis of CRC remains not well‐known. Increasing studies have highlighted the critical roles of long noncoding RNAs (lncRNAs) in tumorigenesis and cancer cells metastasis, however, the expression pattern, biological roles of lncRNAs, and the mechanisms responsible for their function in CRC remain elusive. In this study, we performed a genome‐wide comprehensive analysis of lncRNAs profiling and clinical relevance to identify novel lncRNAs for the further study in CRC. RNA sequencing and microarray data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were annotated and analyzed to find differentially expressed lncRNAs in CRC. Analysis of these datasets revealed that hundreds of lncRNAs expression are dysregulated in CRC tissues when compared with normal tissues. By genomic variation analyses, we identified that some of these lncRNAs dysregulation is associated with the copy number amplification or deletion. Moreover, many lncRNAs expression levels are significantly associated with CRC patients overall and recurrence‐free survivals, such as H19, LEF1‐AS1, and RP11‐296E3.2. Furthermore, we identified one liver metastasis‐associated lncRNA termed LUCAT1 in CRC by analyzing lncRNAs expression profiles in the CRC tissues from patients with liver metastasis compared with the CRC tissues without metastasis. Finally, loss‐of‐function assays determined that knockdown of LUCAT1 could impair CRC cells invasion. Taken together, aberrantly expressed lncRNAs may play critical roles in the development and liver metastasis of CRC, and our findings may provide useful resource for identification of novel biomarkers of CRC.

Long non-coding RNA LUCAT1 is associated with poor prognosis in human non-small lung cancer and regulates cell proliferation via epigenetically repressing p21 and p57 expression.

Recently, long non-coding RNAs (lncRNAs) have been recognized as playing key roles in regulating cellular processes, such as proliferation, invasion, and metastasis. These lncRNAs have been shown to be abnormally expressed in tumorigenic processes. However, the role and clinical relevance of LUCAT1 in non-small-cell lung cancer (NSCLC) remain unclear. In this study, we found that the expression of LUCAT1 was significantly up-regulated in NSCLC tissues compared to non-tumor tissues, and its expression was associated with tumor size, tumor–node–metastasis (TNM) stage and overall survival (OS). Further experiments showed that LUCAT1 knockdown inhibited cell proliferation both in vitro and in vivo. Mechanistic investigations showed that LUCAT1 plays a key role in G0/G1 arrest. We further demonstrated that LUCAT1 was associated with polycomb repressor complexes (PRC2) and that this association was required for epigenetically repression of p21 and p57, thus contributing to the regulation of NSCLC cell cycle and proliferation. In summary, our results show that LUCAT1 could regulate tumorigenesis of NSCLC and be biomarker for poor prognosis in NSCLC.